| Project/Area Number |
59870035
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Pediatrics
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
TADA Keiya Tohoku University School of Medicine, 医学部, 教授 (20046907)
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| Co-Investigator(Kenkyū-buntansha) |
IGARASHI Yutaka Tohoku University School of Medicine, 医学部, 講師 (70101144)
外村 幹雄 鐘紡株式会社, 薬品研究所, 室長
TAKAI Katsuji Tokyo University School of Medicine, 医学部, 教授 (10010000)
SOTOMURA Mikio Kanebo Lt. Co., Research Institute of Medicine
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥25,200,000 (Direct Cost: ¥25,200,000)
Fiscal Year 1986: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1985: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1984: ¥15,300,000 (Direct Cost: ¥15,300,000)
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| Keywords | Phenylalanine-ammonia-lyase (PAL) / Phenylketonuria (PKU) / Intestinal absorption of amino acids and peptide / 腸管灌流モデル / フェニルアラニン・アンモニア・リアーゼ / エンピナーゼ / アラニル・フェニルアラニン / ペプチドの吸収 / 抱括化PAL / ペプタイド / ペプチダーゼ / 連続投与 / PAL |
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| Research Abstract |
Phenylalanine-ammonia-lyase (PAL) strongly catalyses phenylalanine (Phe) to cynnamate. The possibility of oral administration of PAL with mean as a treatment of phenylketonuria (PKU) was studied.
In clinical examination, a patient with PKU was administered 100 U, 300 U, 600 U and 50/kg, respectively, with 50 mg/kg of Phe. The increase of Phe levels in blood were almost same as the increase of blood Phe levels which induced by Phe alone. But, when 50 U/kg of PAl was loaded with 50 mg/kg of Phe, the increments of Phe levels in blood was significantly low as compared with that generated with Phe alone. Another patient with PKU was fed 1 mg/kg of Whey-protein with 30 tablets of PAL included in fibroin and the PAL and Empinase, respectively. The patterns of blood Phe levels were not different with that of Whey alone. He was also tested long-term administration of PAL with meals. The meals contained 24 mg/kg/day of Phe. 30T and PAL included in fibroin were given at each meal. The effect of PAl on serum Phe levels was not seen during 10 days.
We also investigated the effect of PAl with guinea pig. Superior vena cava (SVC) and portal vein (PV) were canurated and small intestine was perfused by Phe and peptids contained Phe with or without PAL. When sufficient PAL was included in the test solution with Phe. The Phe levels in SVC and PV were not so much increase as PAL-free. When peptides were tested, PAL did not show any effect on the Phe levels in SVC and PV.
From this study, we could not get a result that oral administration of PAL with meal was effective to treat patient with PKU.
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